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Editorial overview: Neuroscience: Back to the future in the developing insect nervous system
Available online at www.sciencedirect.com
ScienceDirect Editorial overview: Neuroscience: Back to the future in the developing insect nervous system Susan E Fahrbach Current Opinion in Insect Science 2016, 18:iv–vi For a complete overview see the Issue Available online 5th October 2016 http://dx.doi.org/10.1016/j.cois.2016.10.001 2214-5745/# 2016 Elsevier Inc. All rights reserved.
Susan E Fahrbach
Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA e-mail: [email protected] Susan E Fahrbach is Reynolds Professor of Developmental Neuroscience and Chair of Biology at Wake Forest University in Winston-Salem, NC, USA. Her research focuses on neuroanatomical studies of development and plasticity of the mushroom bodies of the honey bee brain. She is author of a 2013 textbook titled Developmental Neuroscience: A Concise Introduction (Princeton University Press).
When my students happen upon an article on the development of insect nervous systems published in the 1980s or 1990s, they frequently comment that it must have been easier to publish then because each manuscript contains so few experiments relative to today’s data-rich goliaths. It is hard to convince the modern student that the amount of work per manuscript was arguably greater way back when, given the hand-crafted nature of research in developmental biology before the application of computers for image acquisition and data analysis. Despite the appropriately forward looking bias of my students, one of the deep pleasures of a long career in science is the capacity to look back and understand how each successive era builds on previous endeavors. The wonders of one era — P elements! enhancer traps! fluorescent antibodies! bromodeoxyuridine! PCR! (and qRT-PCR!) confocal microscopes! — become everyday research tools, and discoveries that once amazed settle comfortably into review chapters and textbooks. Research fields once new mature. Progress in our understanding of the development of the insect nervous system over the past 30 years has been so substantial that insect developmental neuroscience can be regarded as a mature field. A mature field can afford to take a second look at classic questions with modern methods, and that second look at historically significant questions unites the reviews represented in this issue of Current Opinion in Insect Science. In addition to making full use of innovative methodology, insect neuroscientists have embraced model organisms and comparative approaches with equal enthusiasm. The comfort of insect neuroscientists with this dualism — a combination of the rigorous hypothesis testing attainable in Drosophila melanogaster with a healthy respect for sound phylogenetic reconstruction — is evident in these papers. The accompanying annotated bibliographies blend cutting edge technology and diverse species with a full appreciation of the history of studies of axon guidance, neuronal migration, gliogenesis, live imaging of embryonic development, and neural plasticity. Axon guidance is a classic theme of developmental neuroscience [1]. The function of the nervous system depends upon the formation of appropriate neural circuits, a process that in insects begins in the embryo and continues through larval life as the products of postembryonic neurogenesis extend their axons. The identification, in a large-scale mutant screen, of key Drosophila genes required for growth cones to navigate the midline was the first of numerous studies that have helped us understand the molecular complexity of axon guidance signaling systems, systems in which multiple attractant and repellant ligands interact with multiple receptors [2]. Here Timothy Evans of the University of Arkansas, USA, provides an exciting
Current Opinion in Insect Science 2016, 18:iv–vi
www.sciencedirect.com
Editorial overview Fahrbach v
update to this field. He recounts studies exploring the decision of axons to cross the midline in Drosophila melanogaster, Aedes aegypti, Bombyx mori and Tribolium castaneum. His studies emphatically demonstrate that species other than fruit flies should now be considered genetically tractable, with more likely to come in the near future. Evan’s review raises important questions about how broadly we can generalize specific functions for specific gene products on the basis of observations in a single species. Comparative studies along these lines are required to help us understand what is conserved in the world of axon guidance. Readers intrigued by the SlitRobo signaling described in this review can learn more in by consulting the many recent publications on this classic pathway, including in depth accounts by Evans et al. [3,4]. Sometimes it is not only axons that travel but whole neurons and glial cells [5]. As in the case of extending growth cones, migrating cells must rely on a slew of signals to find their way to their new homes. Philip Copenhaver and Jenna Ramaker of the Oregon Health and Sciences University, USA, have investigated the formation of the enteric nervous system (ENS) of the hawkmoth, Manduca sexta, as a model for study of cell migration during development. The authors carefully outline the evidence supporting a role for the insect ortholog of the amyloid precursor protein (APPL) in the migration of neurons and glia from their sites of origin in the foregut to the midgut. The association of amyloid precursor protein with the neuropathologies of Alzheimer’s disease in humans is widely known [6], but Copenhaver and Ramaker’s account reminds us that this family of proteins is also has regulatory actions in neural development. The authors weave together the results of studies in moth and fruit fly to reach the exciting conclusion that APP family proteins may function as unconventional Goa-coupled receptors that regulate neuronal migration. The comparative theme is sustained in the contribution to this issue by Stelzer and Strobl of the Goethe Universita¨t — Frankfurt am Main, Germany. Once again it is appropriate to use the term exciting to describe the marriage of the comparative approach to the study of embryogenesis with an amazing new tool for data acquisition, light sheet-based fluorescence microscopy [7]. The initial studies of the embryonic development of Tribolium castaneum described in this review are paired with a concise but authoritative introduction to this state-ofthe art technique, which permits long-term non-invasive live imaging with excellent optical penetration of the specimen. This review also contains a compelling defense of the comparative approach to the study of insect development, including a reminder that insect models provided the foundation for the modern field of evo-devo [8]. An appreciation for the function of glial cells in the nervous system of all animals is rising as modern methods www.sciencedirect.com
have led to a reassessment of their functions in both developing and mature nervous systems [9]. Omoto et al. of the University of California, Los Angeles, USA, have provided a review that reminds us that until recently relatively little was known about the origins of glia in the insect nervous system. These authors’ concise account of distinct populations of glia, based upon careful analyses of cell lineage in Drosophila melanogaster, defines the different populations of glial cells (neuropil, surface, cell body, and optic lobe) and clearly distinguishes between primary and secondary gliogenesis. Their review ends with an illuminating discussion of the relationship between insect blood cells (hemocytes) and glia, informed by studies of the properties of vertebrate glia. Of course, two taxa ‘do not a comparative study make,’ [10], but the issues raised in this review provide a strong foundation for exciting comparative studies sure to come, sooner rather than later. At the end of all of the developmental processes lies the adult brain. A long-standing question in studies of neural plasticity is whether the mechanisms of plasticity that support learning and memory are re-purposed mechanisms of development. In some cases, this answer appears to be yes: for example, studies in the mollusk Aplysia have shown that the trans-synaptic adhesive protein interactions that support the formation of synapses during development are similar to those that allow new synapses to form during learning [11]. It is therefore somewhat surprising that studies of synapsin, a protein ubiquitous in presynaptic axon terminals, suggest that a protein of lesser importance during development (based on studies of Drosophila null mutants for synapsin) is a marker of adult synaptic plasticity. My collaborator Van Nest and Fahrbach here provide a review of studies of synapsin immunoreactivity in the mushroom bodies of ant and honey bee that highlights how the use of this marker has the potential to provide new insights into synaptic plasticity in adult insect brains. This method offers a new quantitative approach to the study of the mushroom bodies, an insect brain structure that serves as a center for sensory integration, learning, and memory. The title of this essay derives from a popular science fiction comedy film released in the United States in 1985. The plot is amusingly complicated, featuring a high school student who travels from 1985 to 1955 in a time traveling sports car. Two sequels extended the range of time travel forward to 2015 and back to 1985. The phrase may confuse those who have not enjoyed the silliness of these films, but it captures the ability of researchers in insect developmental neuroscience to re-visit their favorite questions and bring them back to the future with modern research tools. As long as there are developmental neuroscientists and unanswered questions about neural development, the type of time travel that involves bringing the past into the present will never lose its popularity. Current Opinion in Insect Science 2016, 18:iv–vi
vi Neuroscience
References 1.
2.
3.
4.
5.
O’Donnell M, Chance RK, Bashaw GJ: Axon growth and guidance: receptor regulation and signal transduction. Annu Rev Neurosci 2009, 32:383-412. Seeger M, Tear G, Ferres-Marco D, Goodman CS: Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 1993, 10:409-426. Evans TA, Santiago C, Arbeille E, Bashaw GJ: Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons. Elife 2015, 4:e08407. Brown HE, Reichert MC, Evans TA: Slit binding via the Ig1 domain is essential for midline repulsion by Drosophila Robo1 but dispensable for receptor expression, localization, and regulation in vivo. G3 (Bethesda) 2015, 5:2429-2439 http:// dx.doi.org/10.1534/g3.115.022327. Hatten ME: Central nervous system neuronal migration. Annu Rev Neurosci 1999, 22:511-539.
Current Opinion in Insect Science 2016, 18:iv–vi
6.
Selkoe DJ, Hardy J: The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016, 8:595-608.
7.
Keller PJ, Stelzer EH: Quantitative in vivo imaging of entire embryos with digital scanned laser light sheet fluorescence microscopy. Curr Opin Neurobiol 2008, 18:624-632.
8.
Heffer A, Pick L: Conservation and variation in Hox genes: how insect models pioneered the Evo-Devo field. Annu Rev Entomol 2013, 58:161-179.
9.
Zuchero JB, Barres BA: Glia in mammalian development and disease. Development 2015, 142:3805-3809.
10. Garland T Jr, Adolph SC: Why not to do two-species comparative studies: limitations on inferring adaptation. Physiol Zool 1994, 67:797-828. 11. Bailey CH, Kandel ER, Harris KM: Structural components of synaptic plasticity and memory consolidation. Cold Spring Harb Perspect Biol 2015, 7:a021758.
www.sciencedirect.com
ScienceDirect Editorial overview: Neuroscience: Back to the future in the developing insect nervous system Susan E Fahrbach Current Opinion in Insect Science 2016, 18:iv–vi For a complete overview see the Issue Available online 5th October 2016 http://dx.doi.org/10.1016/j.cois.2016.10.001 2214-5745/# 2016 Elsevier Inc. All rights reserved.
Susan E Fahrbach
Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA e-mail: [email protected] Susan E Fahrbach is Reynolds Professor of Developmental Neuroscience and Chair of Biology at Wake Forest University in Winston-Salem, NC, USA. Her research focuses on neuroanatomical studies of development and plasticity of the mushroom bodies of the honey bee brain. She is author of a 2013 textbook titled Developmental Neuroscience: A Concise Introduction (Princeton University Press).
When my students happen upon an article on the development of insect nervous systems published in the 1980s or 1990s, they frequently comment that it must have been easier to publish then because each manuscript contains so few experiments relative to today’s data-rich goliaths. It is hard to convince the modern student that the amount of work per manuscript was arguably greater way back when, given the hand-crafted nature of research in developmental biology before the application of computers for image acquisition and data analysis. Despite the appropriately forward looking bias of my students, one of the deep pleasures of a long career in science is the capacity to look back and understand how each successive era builds on previous endeavors. The wonders of one era — P elements! enhancer traps! fluorescent antibodies! bromodeoxyuridine! PCR! (and qRT-PCR!) confocal microscopes! — become everyday research tools, and discoveries that once amazed settle comfortably into review chapters and textbooks. Research fields once new mature. Progress in our understanding of the development of the insect nervous system over the past 30 years has been so substantial that insect developmental neuroscience can be regarded as a mature field. A mature field can afford to take a second look at classic questions with modern methods, and that second look at historically significant questions unites the reviews represented in this issue of Current Opinion in Insect Science. In addition to making full use of innovative methodology, insect neuroscientists have embraced model organisms and comparative approaches with equal enthusiasm. The comfort of insect neuroscientists with this dualism — a combination of the rigorous hypothesis testing attainable in Drosophila melanogaster with a healthy respect for sound phylogenetic reconstruction — is evident in these papers. The accompanying annotated bibliographies blend cutting edge technology and diverse species with a full appreciation of the history of studies of axon guidance, neuronal migration, gliogenesis, live imaging of embryonic development, and neural plasticity. Axon guidance is a classic theme of developmental neuroscience [1]. The function of the nervous system depends upon the formation of appropriate neural circuits, a process that in insects begins in the embryo and continues through larval life as the products of postembryonic neurogenesis extend their axons. The identification, in a large-scale mutant screen, of key Drosophila genes required for growth cones to navigate the midline was the first of numerous studies that have helped us understand the molecular complexity of axon guidance signaling systems, systems in which multiple attractant and repellant ligands interact with multiple receptors [2]. Here Timothy Evans of the University of Arkansas, USA, provides an exciting
Current Opinion in Insect Science 2016, 18:iv–vi
www.sciencedirect.com
Editorial overview Fahrbach v
update to this field. He recounts studies exploring the decision of axons to cross the midline in Drosophila melanogaster, Aedes aegypti, Bombyx mori and Tribolium castaneum. His studies emphatically demonstrate that species other than fruit flies should now be considered genetically tractable, with more likely to come in the near future. Evan’s review raises important questions about how broadly we can generalize specific functions for specific gene products on the basis of observations in a single species. Comparative studies along these lines are required to help us understand what is conserved in the world of axon guidance. Readers intrigued by the SlitRobo signaling described in this review can learn more in by consulting the many recent publications on this classic pathway, including in depth accounts by Evans et al. [3,4]. Sometimes it is not only axons that travel but whole neurons and glial cells [5]. As in the case of extending growth cones, migrating cells must rely on a slew of signals to find their way to their new homes. Philip Copenhaver and Jenna Ramaker of the Oregon Health and Sciences University, USA, have investigated the formation of the enteric nervous system (ENS) of the hawkmoth, Manduca sexta, as a model for study of cell migration during development. The authors carefully outline the evidence supporting a role for the insect ortholog of the amyloid precursor protein (APPL) in the migration of neurons and glia from their sites of origin in the foregut to the midgut. The association of amyloid precursor protein with the neuropathologies of Alzheimer’s disease in humans is widely known [6], but Copenhaver and Ramaker’s account reminds us that this family of proteins is also has regulatory actions in neural development. The authors weave together the results of studies in moth and fruit fly to reach the exciting conclusion that APP family proteins may function as unconventional Goa-coupled receptors that regulate neuronal migration. The comparative theme is sustained in the contribution to this issue by Stelzer and Strobl of the Goethe Universita¨t — Frankfurt am Main, Germany. Once again it is appropriate to use the term exciting to describe the marriage of the comparative approach to the study of embryogenesis with an amazing new tool for data acquisition, light sheet-based fluorescence microscopy [7]. The initial studies of the embryonic development of Tribolium castaneum described in this review are paired with a concise but authoritative introduction to this state-ofthe art technique, which permits long-term non-invasive live imaging with excellent optical penetration of the specimen. This review also contains a compelling defense of the comparative approach to the study of insect development, including a reminder that insect models provided the foundation for the modern field of evo-devo [8]. An appreciation for the function of glial cells in the nervous system of all animals is rising as modern methods www.sciencedirect.com
have led to a reassessment of their functions in both developing and mature nervous systems [9]. Omoto et al. of the University of California, Los Angeles, USA, have provided a review that reminds us that until recently relatively little was known about the origins of glia in the insect nervous system. These authors’ concise account of distinct populations of glia, based upon careful analyses of cell lineage in Drosophila melanogaster, defines the different populations of glial cells (neuropil, surface, cell body, and optic lobe) and clearly distinguishes between primary and secondary gliogenesis. Their review ends with an illuminating discussion of the relationship between insect blood cells (hemocytes) and glia, informed by studies of the properties of vertebrate glia. Of course, two taxa ‘do not a comparative study make,’ [10], but the issues raised in this review provide a strong foundation for exciting comparative studies sure to come, sooner rather than later. At the end of all of the developmental processes lies the adult brain. A long-standing question in studies of neural plasticity is whether the mechanisms of plasticity that support learning and memory are re-purposed mechanisms of development. In some cases, this answer appears to be yes: for example, studies in the mollusk Aplysia have shown that the trans-synaptic adhesive protein interactions that support the formation of synapses during development are similar to those that allow new synapses to form during learning [11]. It is therefore somewhat surprising that studies of synapsin, a protein ubiquitous in presynaptic axon terminals, suggest that a protein of lesser importance during development (based on studies of Drosophila null mutants for synapsin) is a marker of adult synaptic plasticity. My collaborator Van Nest and Fahrbach here provide a review of studies of synapsin immunoreactivity in the mushroom bodies of ant and honey bee that highlights how the use of this marker has the potential to provide new insights into synaptic plasticity in adult insect brains. This method offers a new quantitative approach to the study of the mushroom bodies, an insect brain structure that serves as a center for sensory integration, learning, and memory. The title of this essay derives from a popular science fiction comedy film released in the United States in 1985. The plot is amusingly complicated, featuring a high school student who travels from 1985 to 1955 in a time traveling sports car. Two sequels extended the range of time travel forward to 2015 and back to 1985. The phrase may confuse those who have not enjoyed the silliness of these films, but it captures the ability of researchers in insect developmental neuroscience to re-visit their favorite questions and bring them back to the future with modern research tools. As long as there are developmental neuroscientists and unanswered questions about neural development, the type of time travel that involves bringing the past into the present will never lose its popularity. Current Opinion in Insect Science 2016, 18:iv–vi
vi Neuroscience
References 1.
2.
3.
4.
5.
O’Donnell M, Chance RK, Bashaw GJ: Axon growth and guidance: receptor regulation and signal transduction. Annu Rev Neurosci 2009, 32:383-412. Seeger M, Tear G, Ferres-Marco D, Goodman CS: Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 1993, 10:409-426. Evans TA, Santiago C, Arbeille E, Bashaw GJ: Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons. Elife 2015, 4:e08407. Brown HE, Reichert MC, Evans TA: Slit binding via the Ig1 domain is essential for midline repulsion by Drosophila Robo1 but dispensable for receptor expression, localization, and regulation in vivo. G3 (Bethesda) 2015, 5:2429-2439 http:// dx.doi.org/10.1534/g3.115.022327. Hatten ME: Central nervous system neuronal migration. Annu Rev Neurosci 1999, 22:511-539.
Current Opinion in Insect Science 2016, 18:iv–vi
6.
Selkoe DJ, Hardy J: The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016, 8:595-608.
7.
Keller PJ, Stelzer EH: Quantitative in vivo imaging of entire embryos with digital scanned laser light sheet fluorescence microscopy. Curr Opin Neurobiol 2008, 18:624-632.
8.
Heffer A, Pick L: Conservation and variation in Hox genes: how insect models pioneered the Evo-Devo field. Annu Rev Entomol 2013, 58:161-179.
9.
Zuchero JB, Barres BA: Glia in mammalian development and disease. Development 2015, 142:3805-3809.
10. Garland T Jr, Adolph SC: Why not to do two-species comparative studies: limitations on inferring adaptation. Physiol Zool 1994, 67:797-828. 11. Bailey CH, Kandel ER, Harris KM: Structural components of synaptic plasticity and memory consolidation. Cold Spring Harb Perspect Biol 2015, 7:a021758.
www.sciencedirect.com